ErbB receptor tyrosine kinase/NF-κB signaling controls mammosphere formation in human breast cancer

• DOI: 10.1073/pnas.1113271109
• Publication Date: 2012-04-06T05:04:43Z
• Authors: Kunihiko Hinohara; Seiichiro Kobayashi; Hajime Kanauchi; Seiichiro Shimizu; Kotoe Nishioka; Ei-ichi Tsuji; Kei-ichiro Tada; Kazuo Umezawa; Masaki Mori; Toshihisa Ogawa; Jun-ichiro Inoue; Arinobu Tojo; Noriko Gotoh
• Keywords: ErbB; ERBB3; Neuregulin; neuregulin 1

Breast cancer is one of the most common cancers in humans. However, our understanding cellular and molecular mechanisms underlying tumorigenesis breast tissues limited. Here, we identified a mechanism that controls ability cells to form multicellular spheroids (mammospheres). We found heregulin (HRG), ligand for ErbB3, induced mammosphere formation stem cell (BCSC)–enriched population as well lines. HRG-induced was reduced by treatment with inhibitors phosphatidyl inositol 3-kinase (PI3K) or NF-κB expression IκBα-Super Repressor (IκBαSR), dominant-negative inhibitor NF-κB. Moreover, overexpression IκBαSR inhibited NOD/SCID mice. Furthermore, IL8, regulator self-renewal BCSC-enriched populations, HRG through activation PI3K/NF-κB pathway. These findings illustrate HRG/ErbB3 signaling appears maintain pathway human cancer.